| Sumario: | Background Frailty reflects systemic vulnerability and is a major public health concern in ageing. This study examined how frailty relates to risk of death, hospitalisation and major chronic diseases. Methods We analysed data from 20 975 adults (≥35 years, 52% women) recruited in 2005–10 from the population-based Moli-sani Study (Italy) and followed for a median of 15 years. Frailty was assessed using a multidimensional 29-item frailty index (FI). Cox models accounting for competing risks estimated hazard ratios (HR) for 17 incident outcomes, adjusted for age, sex and common covariates, including social status indicators. Results Frailty was associated with increased risk of several adverse outcomes. Per 1-SD increase in FI, the risk of type-2 diabetes and coronary heart disease rose by 82% (HR = 1.82; 95% confidence interval 1.73–1.92; 1541 events) and 33% (HR = 1.33; 1.23–1.44; 756). FI was also associated with an increased risk of Parkinson's disease (HR = 1.25; 1.05–1.47; 158) and non-Alzheimer dementia (HR = 1.31; 1.11–1.54; 150). Cancer associations varied by site. FI also predicted hospitalisations for any cause (HR = 1.31; 1.28–1.34; 11 193), and all-cause mortality (HR = 1.35; 1.30–1.40; 2631). Analyses comparing frail and prefrail with fit categories, excluding early events, and stratified by sex showed consistent results, with indications of somewhat stronger associations among individuals younger than 65 years in certain outcomes. Conclusion FI predicts a wide range of chronic diseases, especially cardiometabolic and neurodegenerative outcomes, and their negative consequences, including hospitalisation and mortality. These findings reinforce the importance of frailty assessment in preventive strategies, risk stratification and integrated surveillance in the general population.
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